The long-term objective is to understand the eukaryotic nucleus, using the yeast, Saccharomyces cerevisiae, as a model system. The overall aim is to identify genes affecting structure and function in the nucleus. Current effort is focused in three areas. 1) the mechanism of transcriptional silencing of the mating type loci and telomeres. This silencing is thought to be due to the yeast equivalent of heterochromatin. A novel genetic screen has identified a number of new genes that appear to play a role in silencing. The functions of these genes will be investigated. One of the genes encodes a protein that binds to SIR4; the possibility that this binding is responsible for bringing silent chromatin to the nuclear periphery will be tested. 2) a study of the evolutionarily conserved gene, ASF1. The function of this protein in the nucleus is unknown. It may play a role in repair of DNA damage in chromatin. The two-hybrid system, genetic screens and biochemical methods will be used to find proteins that interact with ASF1. 3) a study of an essential gene, HBP3, and its possible role in chromatin remodeling or histone deposition during DNA replication. Progress in these areas will shed light on chromosome structure and function in the eukaryotic nucleus, not only in yeast but also in mammalian cells.